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GeneBe

3-127695038-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_007283.7(MGLL):c.753A>G(p.Leu251=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0947 in 1,613,990 control chromosomes in the GnomAD database, including 7,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 950 hom., cov: 32)
Exomes 𝑓: 0.094 ( 6903 hom. )

Consequence

MGLL
NM_007283.7 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0500
Variant links:
Genes affected
MGLL (HGNC:17038): (monoglyceride lipase) This gene encodes a serine hydrolase of the AB hydrolase superfamily that catalyzes the conversion of monoacylglycerides to free fatty acids and glycerol. The encoded protein plays a critical role in several physiological processes including pain and nociperception through hydrolysis of the endocannabinoid 2-arachidonoylglycerol. Expression of this gene may play a role in cancer tumorigenesis and metastasis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-127695038-T-C is Benign according to our data. Variant chr3-127695038-T-C is described in ClinVar as [Benign]. Clinvar id is 3056921.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.05 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MGLLNM_007283.7 linkuse as main transcriptc.753A>G p.Leu251= synonymous_variant 7/8 ENST00000265052.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MGLLENST00000265052.10 linkuse as main transcriptc.753A>G p.Leu251= synonymous_variant 7/81 NM_007283.7

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.106
AC:
16194
AN:
152082
Hom.:
950
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.160
Gnomad AMI
AF:
0.0362
Gnomad AMR
AF:
0.0860
Gnomad ASJ
AF:
0.0793
Gnomad EAS
AF:
0.00907
Gnomad SAS
AF:
0.0770
Gnomad FIN
AF:
0.0582
Gnomad MID
AF:
0.0696
Gnomad NFE
AF:
0.0980
Gnomad OTH
AF:
0.0989
GnomAD3 exomes
AF:
0.0839
AC:
20936
AN:
249476
Hom.:
1074
AF XY:
0.0851
AC XY:
11520
AN XY:
135382
show subpopulations
Gnomad AFR exome
AF:
0.160
Gnomad AMR exome
AF:
0.0516
Gnomad ASJ exome
AF:
0.0821
Gnomad EAS exome
AF:
0.0101
Gnomad SAS exome
AF:
0.0774
Gnomad FIN exome
AF:
0.0609
Gnomad NFE exome
AF:
0.101
Gnomad OTH exome
AF:
0.0901
GnomAD4 exome
AF:
0.0935
AC:
136682
AN:
1461790
Hom.:
6903
Cov.:
32
AF XY:
0.0933
AC XY:
67847
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.162
Gnomad4 AMR exome
AF:
0.0559
Gnomad4 ASJ exome
AF:
0.0810
Gnomad4 EAS exome
AF:
0.00680
Gnomad4 SAS exome
AF:
0.0779
Gnomad4 FIN exome
AF:
0.0644
Gnomad4 NFE exome
AF:
0.0992
Gnomad4 OTH exome
AF:
0.0912
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.106
AC:
16198
AN:
152200
Hom.:
950
Cov.:
32
AF XY:
0.102
AC XY:
7575
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.160
Gnomad4 AMR
AF:
0.0859
Gnomad4 ASJ
AF:
0.0793
Gnomad4 EAS
AF:
0.00909
Gnomad4 SAS
AF:
0.0768
Gnomad4 FIN
AF:
0.0582
Gnomad4 NFE
AF:
0.0981
Gnomad4 OTH
AF:
0.0978
Alfa
AF:
0.0946
Hom.:
950
Bravo
AF:
0.111
Asia WGS
AF:
0.0570
AC:
200
AN:
3478
EpiCase
AF:
0.0963
EpiControl
AF:
0.106

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

MGLL-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJan 02, 2020This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
8.6
Dann
Benign
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4881; hg19: chr3-127413881; COSMIC: COSV54024486; API